Randomized Phase 3 Trial of Triple Combination of Induction, Concurrent and Adjuvant Chemotherapy Versus Concurrent Chemotherapy Alone in High Risk Nasopharyngeal Carcinoma Patients Treated With Intensity-modulated Radiotherapy
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 534
- 试验地点
- 1
- 主要终点
- failure-free survival
研究概览
简要总结
The investigators aim to evaluate the survival benefit from triple combination of induction, concurrent and aduvant chemotherapy versus concurrent chemotherapy alone for high risk locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.
详细描述
All eligible patients receive intensity-modulated radiotherapy (IMRT) with a total dose of 68 to 70 Gy in 33 fractions to the primary tumor. Patients in the experimental arm receive triple therapy of induction, concurrent and adjuvant chemotherapy. Induction chemotherapy consists of docetaxel 75 mg/m², D1 and cisplatin 25 mg/m², D1-3 every 3 weeks for 2 cycles. Concurrent chemotherapy in the experimental arm consists of cisplatin 25 mg/m², D1-3 every 3 weeks and Xeloda 2000mg/m², D1-14 for 3 cycles. Adjuvant chemotherapy consists of Xeloda 2500mg/m², D1-14 for 2 cycles. Concurrent chemotherapy in the control arm consists of cisplatin 100 mg/m², D1 every 3 weeks for 3 cycles.The primary endpoint is failure-free survival (FFS). Secondary end points include overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and the incidence of grade 3 or higher acute toxicities. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly histologically confirmed non-keratinizing (WHO 1991) nasopharyngeal carcinoma.
- •Tumor staged as T4N0-3M0 or T1-3N3M0 (the 2010 UICC/AJCC staging system).
- •Pretreatment EBV DNA ≥ 4000 copies/mL.
- •Karnofsky scale (KPS) ≥
- •Adequate marrow: leucocyte count ≥ 4×10E9/L, hemoglobin ≥ 110g/L and platelet count ≥ 100×10E9/L.
- •Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and bilirubin ≤ 1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) ≤ 2.5×ULN.
- •Adequate renal function: creatinine clearance ≥ 60 ml/min or creatinine ≤ 1.5×ULN.
- •Patients must give written informed consent.
排除标准
- •Prior malignancy, except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
- •Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period).
- •History of previous radiotherapy (except for non-melanomatous skin cancers outside intended radiotherapy volume).
- •Prior radiotherapy, chemotherapy or surgery (except diagnostic) to primary tumor or nodes.
- •Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose > 1.5×ULN), and emotional disturbance.
- •Dihydropyrimidine dehydrogenase deficiency.
研究组 & 干预措施
IC plus CC plus IMRT plus AC
Induction chemotherapy: TP -- Docetaxel 75mg/m2, D1 and cisplatin 25 mg/m2, D1-3 every 3 weeks for 2 cycles; Concurrent chemotherapy: PX -- Cisplatin 25 mg/m2, D1-3 and Xeloda 2000mg/m2, D1-14, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy; Adjuvant chemotherapy: Xeloda 2500mg/m2, D1-14, every 3 weeks for 2 cycles
干预措施: Cisplatin 1 (Drug)
IC plus CC plus IMRT plus AC
Induction chemotherapy: TP -- Docetaxel 75mg/m2, D1 and cisplatin 25 mg/m2, D1-3 every 3 weeks for 2 cycles; Concurrent chemotherapy: PX -- Cisplatin 25 mg/m2, D1-3 and Xeloda 2000mg/m2, D1-14, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy; Adjuvant chemotherapy: Xeloda 2500mg/m2, D1-14, every 3 weeks for 2 cycles
干预措施: Docetaxel (Drug)
IC plus CC plus IMRT plus AC
Induction chemotherapy: TP -- Docetaxel 75mg/m2, D1 and cisplatin 25 mg/m2, D1-3 every 3 weeks for 2 cycles; Concurrent chemotherapy: PX -- Cisplatin 25 mg/m2, D1-3 and Xeloda 2000mg/m2, D1-14, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy; Adjuvant chemotherapy: Xeloda 2500mg/m2, D1-14, every 3 weeks for 2 cycles
干预措施: Xeloda (Drug)
IC plus CC plus IMRT plus AC
Induction chemotherapy: TP -- Docetaxel 75mg/m2, D1 and cisplatin 25 mg/m2, D1-3 every 3 weeks for 2 cycles; Concurrent chemotherapy: PX -- Cisplatin 25 mg/m2, D1-3 and Xeloda 2000mg/m2, D1-14, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy; Adjuvant chemotherapy: Xeloda 2500mg/m2, D1-14, every 3 weeks for 2 cycles
干预措施: Intensity-modulated radiotherapy (Radiation)
CC plus IMRT
Concurrent chemotherapy: Cisplatin 100 mg/m2, D1, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy
干预措施: Cisplatin 2 (Drug)
CC plus IMRT
Concurrent chemotherapy: Cisplatin 100 mg/m2, D1, every 3 weeks for 3 cycles; Radiation: Intensity-modulated radiotherapy
干预措施: Intensity-modulated radiotherapy (Radiation)
结局指标
主要结局
failure-free survival
时间窗: Two year
次要结局
- overall survival(two year)
- distant metastasis-free survival(two year)
- locoregional relapse-free survival(two year)
- Number of participants with treatment-related acute adverse events as assessed by CTCAE v4.0(two months)
研究者
Fang-Yun Xie
Prof.
Sun Yat-sen University